Numerous species of arthropods are parasitic, and many play a role in transmission of disease. Indeed, parasitic arthropods and the diseases they transmit are a global problem. Ecto-parasitic arthropods such as, e.g., ticks, mites, flies, fleas, midges, suck blood from their hosts and in the process, can act as vectors for protozoan, rickettsial and viral pathogens. Thus, the presence of ecto-parasitic arthropods is frequently associated with disease.
Among the ecto-parasitic arthropods, ticks are particularly problematic and harmful. Indeed, ticks are second only to mosquitoes as vectors of human disease, both infectious and toxic. Hard ticks (Ixodidae) can transmit human diseases such as e.g., relapsing fever, Lyme disease, Rocky Mountain spotted fever, tularemia, equine encephalitis, Colorado tick fever, and several forms of ehrlichiosis. Additionally, they are responsible for transmitting livestock and pet diseases, including babesiosis, anaplasmosis and cytauxzoonosis.
Because of their ability to transmit diseases to humans and animals, the medical and economic importance of ticks has long been recognized. Economic losses associated with ticks are typically manifest through their adverse effects on their livestock hosts. See e.g., L'Hostis M, Seegers H. (2002) Vet Res. 33(5):599-611; Peter, R. J., et al. (2005) Vet Parasitol. 132(3-4):205-215. In addition to being disease vectors, blood sucking by large numbers of ticks can cause a loss of blood in the host animal. This, in turn, can result in a reduction in live weight, and may even result in anemia. Still more, multiple tick bites can reduce the quality of hides. Thus, ticks affect the product performance of livestock.
Ticks and tick-borne diseases are important in all domestic animals, but the development and production of innovative tick control methods have been focused primarily on the economically important tick-borne diseases of cattle. Indeed, the tick borne protozoan Babesia parasites remain an important limitation for development of cattle industries worldwide. Effective control of Babesia and other tick borne diseases will certainly require eradication of the tick vectors as well as vaccination against the Babesia parasites.
Given the impact tick infestations can have on livestock, it is not surprising that numerous methods for tick control have been attempted see e.g., U.S. Pat. No. 6,103,758, U.S. Pat. No. 6,331,297, U.S. Pat. No. 6,100,501 and U.S. Pat. No. 5,587,311. Unfortunately however, every method so far developed has shortcomings that limit wide application of the method.
For example, chemical acaricides have traditionally been the first line defense against ticks, and do show efficacy. Unfortunately however, the use of chemical acaricides has numerous drawbacks, including, but not limited to the development of chemical resistant tick strains, the presence of residues in the milk and meat, and harmful effects on the animals being treated, human beings, and the environment (see e.g., Nolan J. (1990) Parasitol. 32:145-153; George J. E., et al. (2004) Parasitology. 129(7):5353-5366; Wharton, R. H., and Roulston, W. J. (1970) Annu Rev Entomol. 15(1):381-405; and U.S. Department of Agriculture. Agriculture Handbook, No. 321. Washington, D.C.: 1967. Safe Use of Agricultural and Household Pesticides; p. 65.).
Because of the problems associated with use of chemical acaricide products, alternative methods for tick control have also been used and/or tested. For example, resistance to tick infestation varies among individual animals and among different breeds of cattle (see e.g., Latif, A. A., and Pegram, R. G. (1992) Insect Sci & Appl. 13:505-513). Therefore, breeding of tick resistant cattle has been attempted (see e.g., Wharton, R. H. (1983) Wld Anim Rev, (FAO). 36:34-41). However, despite the attractiveness of this approach to tick control, selective breeding for tick resistance is difficult, unpredictable, and time consuming. Indeed, each animal still develops its own level of resistance in response to tick challenge and a wide range of resistance occurs. Resistance can only be tested by exposing the putatively resistant animals to ticks, and then resistance can only be measured in terms of average number of ticks per animal. Thus, development of new resistant breeds is a time consuming process with limited usefulness.
Despite the difficulties associated with breeding resistant livestock strains, the idea of tick resistant animals remains attractive. Therefore, attempts have been made to achieve resistance through vaccination. Indeed, a number of vaccines against ticks and tick-borne diseases have been developed or are in the course of being developed. Vaccines have utilized complex tick extracts to stimulate an acquired immunity (see e.g., Willadsen, P., and Kemp, D. H. (1988) Parasitol Today. 4(7):196-198). And, isolated tick proteins such as Bm86, and Bm95 have been used for the production of recombinant vaccines (see e.g., Willadsen, P., et al. (1988) Int J Parasitol. 18(2):183-189; Rand, K. N., et al. (1989) Proc Natl Acad Sci USA. December; 86(24):9657-61; Garcia-Garcia, J. C., et al. (2000) Vaccine. 18(21):2275-2287; Willadsen P. (2004) Parasitology 129 Suppl:S367-87 Review; and de la Fuente, J. et al. (1999) Genet Anal. 15(3-5):143-8. Review).
Unfortunately however, widespread use of recombinant vaccines is limited by a number of factors. First, vaccines, recombinant or otherwise, must be produced in large fermentors. Recombinant proteins and/or other antigens must be isolated, typically requiring cumbersome methods, and the isolated antigens may not be completely pure. Furthermore, the vaccines in use today typically require multiple inoculations per year. Even with multiple inoculations, the available vaccines do not achieve 100% efficiency, and so other control measures e.g., the use of acaracides, need to used in combination with the vaccine for full control of the ticks.
Nevertheless, immunity to parasitic arthropods e.g., ticks, is a highly desired form of parasite control. Indeed, what is needed in the art is an effective vaccine that would provide sustained and effective immunological response with a single inoculation. Such a vaccine would avoid the problems associated with acaricide resistance, chemical residues in food and the environment, and the difficulty of breeding tick resistant species for all animal production systems. Fortunately, as will be clear from the following disclosure, the present invention provides for this and other needs.